Multiple sclerosis (MS), also known as disseminated sclerosis or encephalomyelitis disseminata, is a demyelinating disease in which the insulating covers of nerve cells in the brain and spinal cord are damaged. This damage disrupts the ability of parts of the nervous system to communicate, resulting in a wide range of signs and symptoms, including physical, mental, and sometimes psychiatric problems.
MS takes several forms, with new symptoms either occurring in isolated attacks (relapsing forms) or building up over time (progressive forms). Between attacks, symptoms may disappear completely; however, permanent neurological problems often occur, especially as the disease advances.
MS is the most common autoimmune disorder affecting the central nervous system.
To date, there is no known cure or prophylactic treatment for MS. Treatments attempt to improve function after an attack and prevent new attacks. Medications used to treat MS, while modestly effective, can have adverse effects and be poorly tolerated. Corticosteroids, such as oral prednisone and intravenous methylprednisolone, are prescribed to reduce nerve inflammation. Other treatments for relapsing-remitting MS include beta interferons, glatiramer acetate (Copaxone), Dimethyl fumarate (Tecfidera), fingolimod (Gilenya), teriflunomide (Aubagio), natalizumab (Tysabri), alemtuzumab (Lemtrada) and mitoxantrone. Many people pursue alternative treatments, despite a lack of evidence.
During the 2000s and 2010s, several oral drugs have been approved. Other oral drugs are under investigation, including ozanimod and laquinimod. Laquinimod was announced in August 2012 and is in a third phase III trial after mixed results in the previous ones. Similarly, studies aimed to improve the efficacy and ease of use of already existing therapies are being carried out. This includes the use of new preparations or derivatives of known drugs such as the PEGylated version of interferon-β-1a.
Monoclonal antibodies have also raised interest. Alemtuzumab, daclizumab, and CD20 monoclonal antibodies such as rituximab, ocrelizumab, ofatumumab or anti HERV W Env are thought to be of some benefit and are under study as potential treatments. Their use has often been accompanied by the appearance of potentially dangerous adverse effects, the most important of which being opportunistic infections.
Another research strategy is to evaluate the combined effectiveness of two or more drugs. The main rationale for using a number of medications in MS is that the involved treatments target different mechanisms and, therefore, their use is not necessarily exclusive. Synergies are also possible, but there can also be drawbacks such as the blocking of the action of the partner medication or worsened side-effects.
There is still an unmet need in the art for prophylactic or therapeutic agents able to prevent, delay the onset and/or treat multiple sclerosis, in particular relapsing-remitting multiple sclerosis (RRMS). All treatment options are of potential great value for MS: prophylactic (before onset of symptoms), semi-therapeutic (at the start of the clinically defined disease) or therapeutic (during the course of the disease). Since there is no known marker for the sub-clinical manifestations of the disease (before the onset of the recognized symptoms, often visual manifestations) all treatment regimens likely to be adopted will be of therapeutic nature, destined at decreasing the intensity of the disease or delaying its time course or clinical evolution.
Fowler's solution is a solution containing 1% potassium arsenite (KAsO2), and was once prescribed as a remedy or a tonic. From 1845, Fowler's solution was used as a leukemia treatment.
As some arsenical compounds are notably toxic and carcinogenic, with side effects such as cirrhosis of the liver, idiopathic portal hypertension, urinary bladder cancer, and skin cancers, Fowler's solution fell from use.
Interest in arsenic compounds returned with the use of Arsenic Trioxide (As2O3) as an anti-cancer (“antineoplastic” or “cytotoxic”) chemotherapy. It has been approved by the US FDA for the treatment of acute promyelocytic leukemia that is unresponsive to “first line” agents, namely all-trans retinoic acid (ATRA). It has been shown that arsenic trioxide induces cancer cells to undergo apoptosis. The combination therapy of arsenic trioxide and all-trans retinoic acid (ATRA) has been approved by the U.S. Food and Drug Administration (FDA) for the treatment of acute promyelocytic leukemia.
Bobé et al. (Blood, 108, 13, p 3967-3975, 2006) investigated the effects of arsenic trioxide in a mouse model of systemic lupus erythematosus. As2O3 significantly prolonged survival of MRL/lpr mice by preventing young mice from developing the syndrome and quasi-totally reversing established disease in older animals. These authors suggested that this compound might be useful in the treatment of autoimmune diseases such as lupus erythematosus.
However, it has not yet been demonstrated that arsenic trioxide could be used in the treatment or prevention of multiple sclerosis, which is a specific autoimmune disease targeting the central nervous system.